{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:17:48Z","timestamp":1762100268160},"reference-count":46,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:p> Calmodulin (CaM) is implicated in regulation of Ca<jats:sup>2+<\/jats:sup> channels as a Ca<jats:sup>2+<\/jats:sup> sensor. The effect of CaM on rundown of L-type Ca<jats:sup>2+<\/jats:sup> channels in inside-out patch form was investigated in guinea pig ventricular myocytes. Ca<jats:sup>2+<\/jats:sup> channel activity disappeared within 1\u20133 min and did not reappear when the patch was excised and exposed to an artificial intracellular solution. However, application of CaM (0.03, 0.3, 3 \u03bcM) + 3 mM ATP to the intracellular solution within 1 min after patch excision resulted in dose-dependent activation of channel activity. Channel activity averaged 11.2%, 94.7%, and 292.9%, respectively, of that in cell-attached mode. Channel activity in inside-out patch mode was induced by CaM + ATP at nanomolar Ca<jats:sup>2+<\/jats:sup> concentrations ([Ca<jats:sup>2+<\/jats:sup>]); however, increase to micromolar [Ca<jats:sup>2+<\/jats:sup>] rapidly inactivated the channel activity induced, revealing that the effect of CaM on the channel was Ca<jats:sup>2+<\/jats:sup> dependent. At the 2nd, 4th, 6th, 8th, and 10th minutes after patch excision, CaM (0.75 \u03bcM) + ATP induced Ca<jats:sup>2+<\/jats:sup> channel activity to 150%, 100%, 96.9%, 29.3%, and 16.6%, respectively, revealing a time-dependent action of CaM on the channel. CaM added with adenosine 5\u2032-(\u03b2,\u03b3-imido)triphosphate (AMP-PNP) also induced channel activity, although with much lower potency and shorter duration. Protein kinase inhibitors KN-62, CaM-dependent protein kinase (CaMK)II 281-309, autocamtide-related CaMKII inhibitor peptide, and K252a (each 1\u201310 \u03bcM) did not block the effect of CaM, indicating that the effect of CaM on the Ca<jats:sup>2+<\/jats:sup> channel was phosphorylation independent. Neither CaM nor ATP alone induced Ca<jats:sup>2+<\/jats:sup> channel activity, showing a cooperative effect of CaM and ATP on the Ca<jats:sup>2+<\/jats:sup> channel. These results suggest that CaM is a crucial regulatory factor of Ca<jats:sup>2+<\/jats:sup> channel basal activity. <\/jats:p>","DOI":"10.1152\/ajpcell.00105.2004","type":"journal-article","created":{"date-parts":[[2004,11,3]],"date-time":"2004-11-03T17:58:44Z","timestamp":1099504724000},"page":"C1717-C1724","source":"Crossref","is-referenced-by-count":36,"title":["Calmodulin reverses rundown of L-type Ca<sup>2+<\/sup> channels in guinea pig ventricular myocytes"],"prefix":"10.1152","volume":"287","author":[{"given":"Jian-Jun","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Ying","family":"Hao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asako","family":"Kameyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Kameyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","unstructured":"Anderson ME, Braun AP, Wu YJ, Lu T, Wu YM, Schulman H, and Sung RJ. 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